The brachial plexus is a network of nerves formed by the ventral rami of the four lower cervical nerves (C5, C6, C7, C8) and the first thoracic nerve (T1), with some variability amongst different species. Brachial plexus injury (BPI) is a nerve injury defined by loss of function in one or both upper limbs resulting from partial or complete denervation of muscles. A BPI may occur when this network of nerves is compressed, stretched, or, in more serious cases, avulsed. Approximately 1.2% of multi-trauma patients suffer from some form of BPI, and the majority of these injuries are caused by high velocity traffic collisions . Adult patients with BPI are, on average, young men between the ages of 25 and 29 and go on to suffer socioeconomic disadvantages, physical disabilities, and a decreased quality of life [2–4].
BPI can restrict upper limb function in a variety of ways. Injury to C5-C6 nerves causes loss of elbow flexion, shoulder abduction, and external rotation. Deficits in movements of the fingers and wrist indicate involvement of C7 and C8 spinal nerves . Sensory and motor deficits are accompanied by neuropathic pain in up to 95% of BPIs and can be extremely debilitating [6, 7]. Secondary signaling cascades, including inflammation, oxidative stress, blood-spinal cord barrier destruction, and scar formation, further exacerbate the injury and negatively impact recovery [8–11].
Treatment for BPI has been unsatisfactory due to the complexity of the injury and the lack of specific treatments . Brachial plexus avulsion (BPA) is a preganglionic lesion and is the most severe form of BPI; it is extremely difficult to treat . Current treatment methods of BPI include distal nerve transfers, brachial plexus exploration, nerve grafting from residual nerves, free muscle transfers, and tendon transfers . Despite recent advances in nerve repair techniques, the prognosis of BPA, especially panplexus injuries, is generally poor [5, 14].
Highly translatable animal models are required to recapitulate the anatomy and complex pathophysiology associated with BPI. Rats and mice are the most-often studied animal model and represent a majority of scientific literature. These models are low cost, have well-established analysis methods, and have easily manageable husbandry. However, these studies fail to produce satisfactory results in human clinical trials, likely due to differences in size, physiological responses, and anatomy . A lack of comparative studies on descending neural pathways, differences in segmental injury distribution, and difficulty estimating international treatment standards also contribute to the failure of clinical trials [17, 18]. These limitations may be more easily overcome with a better intermediary animal model. Larger animals such as swine have shown to be a valuable translational resource for modeling more complex pathophysiology. Similarities in body size, physiological responses, and anatomical dimensions to humans make swine an excellent translational model . Conventional breeds of pigs typically reach 100 kg by 4 months of age and 249–306 kg at full maturity and are impractical for use in long-term studies. In contrast, the Wisconsin Miniature Swine™ (WMS™) range from 25–50 kg at 4 months of age and 68–91 kg at full maturity, approximating the weight of an average human, and can be maintained at adult human size for years . The low cost, short gestation interval, and high availability of swine are also advantages over the non-human primate models that are traditionally more costly. Swine share ten times the number of orthologous gene families with humans compared to rodent models and have an analogous inflammatory marker profile post-injury [20, 21]. Similarities between swine and humans in dietary structure, kidney function, respiratory rates, and social behaviors further advance their suitablility as a medical animal model . Swine have more recently been used for translational research in cardiology, diabetes, traumatic brain injury, and spinal cord injury [23–26]. The purpose of this study is to perform an in-depth anatomical comparison of the brachial plexus between humans and WMS to determine suitability as a model for BPI treatment research.